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Neurochemical markers of human fungiform papillae and taste buds.

The presence of distribution of several neurochemical markers in human fungiform papillae and taste buds were investigated by the immunohistochemical technique. The gustatory cells of the taste buds are in synaptic contact with sensory nerve endings, and considering the taste buds strictly as specialized sensory organs, the amounts and distribution of some of the neurochemical markers were different to what we expected. For example, few structures showed immunoreactivity to the tachykinins substance P (SP), calcitonin gene-related peptide (CGRP), and neurokinin A (NKA) also for the peptides vasoactive intestinal polypeptide (VIP), neuropeptide tyrosine (NPY) and galanin, low amounts of immunoreactivity occurred. On the other hand, using antibodies to protein gene product 9.5 (PGP 9.5), protein S-100, and glutamate, numerous nerve fibres and/or immunoreactive cells were found in the fungiform papillae, in the epithelium, in the connective tissue and around blood vessels, as well as in or near taste buds. Incubation with the antibodies against somatostatin, enkephalin, bombesin, peptide histidine isoleucine amide (PHI), cholecystokinin (CCK)/gastrin and dopamine-beta-hydroxylase (DBH) was negative for the fungiform papillae. In conclusion, the present study has shown several immunoreactive structures using antibodies against certain neurochemical markers. Further investigations will hopefully correlate these morphological findings with functional taste perception data. Future studies of patients with taste disorders or other pathological changes correlated with taste and tongue will also be of utmost importance.

Antibodies↗

Neural mechanisms of taste aversion learning.

When ingestion of a taste stimulus is paired with internal malaise the animal remembers the taste and rejects its ingestion thereafter. A model of neural substrate for this conditioned taste aversion (CTA) is presented on the basis of our recent experiments. To establish the CTA in rats, 0.01 M saccharin was paired with i.p. injection of 0.15 M LiCl. Behavioral lesion experiments by means of ibotenic acid showed that the parabrachial nucleus (PBN), medial thalamus (MT), and lateral part of the amygdala (LPA) were crucial to establish the CTA. c-fos immunoreactivity studies showed that ingestion of saccharin induced a remarkable activation of the central lateral (cl) subnucleus of the PBN in normal rats, however, rats with the CTA to saccharin showed c-fos neurons in the ventral lateral (vl) subnucleus of the PBN. These findings suggest that the recipient zone for saccharin taste switches from the cl to vl subnuclei after acquisition of a CTA. The taste pathway from the vl subnucleus to the LPA through the MT may be a neural substrate for taste aversion learning. The switching may result from a plastic change involving long-term potentiation and depression due to a convergence of the taste input of saccharin and general visceral information of LiCl injection.

Animals↗

Anatomical location of a taste-related region in the thalamic reticular nucleus in rats.

To locate a taste-related region in the thalamic reticular nucleus (Rt), we explored a reticular region having connections with the thalamic taste relay and the cortical taste area (CTA), by neuronal tracing methods using HRP, WGA-HRP and biocytin. Tracer injections at the thalamic taste relay, i.e., the parvicellular part of the thalamic posteromedial ventral nucleus (VPMpc), labeled cell bodies and axon terminals in a confined portion of the ipsilateral Rt. This was located at the ventromedial-most portion of the nucleus at the level of approx. 1.2 mm rostral to the rostral end of the VPMpc. Tracer injections at the CTA ipsilaterally labeled axon terminals in the same region of the Rt, as did the thalamic injections. When WGA-HRP was injected at this taste-related region in the Rt, we observed labeled cell bodies in layer VI in the CTA; in the VPMpc we saw densely labeled axon terminals but few, if any, labeled cell bodies. The results indicated that the taste-related region in the Rt receives input from the VPMpc and CTA, and sends output to the VPMpc. They also showed that the reticulo-thalamic projections were much heavier than the thalamo-reticular ones in the taste system.

Afferent Pathways↗

Vasoactive intestinal peptide-like immunoreactivity in rodent taste cells.

The neuropeptide vasoactive intestinal peptide was localized to taste buds of the posterior tongue regions of hamsters and rats by immunocytochemical techniques. Tissue sections, taken from foliate and circumvallate papillae, generally revealed taste buds in which all cells were immunoreactive; however, occasionally some taste buds were found to contain highly reactive individual cells adjacent to non-reactive cells. Additionally, some non-reactive taste buds were observed. Taste buds that displayed vasoactive intestinal peptide-like immunoreactivity usually had a tendency for much darker staining at the apical ends of the cells than the basal ends, suggesting a polar cytoplasmic distribution of the peptide. The multi-functional roles of vasoactive intestinal peptide in other physiological systems combined with both its cytoplasmic localization in taste cells and the known histochemistry/ultrastructure of taste cells raises interesting speculations of this peptide's function in gustation that include secretion, stimulation of a second messenger system, and neuromodulation.

Animals↗

Multimodal responses of taste neurons in the frog nucleus tractus solitarius.

The responses of 216 neurons in the nucleus tractus solitarius (NTS) of the American bullfrog were recorded following taste, temperature, and tactile stimulation. Cells were classified on the basis of their responses to 5 taste stimuli: 0.5 M NaCl, 0.0005 M quinine-HCl (QHCl), 0.01 M acetic acid, 0.5 M sucrose, and deionized water (water). Neurons showing excitatory responses to 1, 2, 3, or 4 of the 5 kinds of taste stimuli were named Type I, II, III, or IV, respectively. Cells whose spontaneous rate was inhibited by taste and/or tactile stimulation of the tongue were termed Type V. Type VI neurons were excited by tactile stimulation alone. Of the 216 cells, 115 were excited or inhibited by taste stimuli (Types I-V), with 35 being Type I, 34 Type II, 40 Type III, 2 Type IV and 4 Type V. The remaining 101 cells were responsive only to tactile stimulation (Type VI). Of those 111 cells excited by taste stimulation (Types I-IV), 106 (95%) responded to NaCl, 66 (59%) to acetic acid, 44 (40%) to QHCl, 10 (9%) to water, and 9 (8%) to warming. No cells responded to sucrose. Of the 111 cells of Types I-IV, 76 (68%) were also sensitive to mechanical stimulation of the tongue. There was some differential distribution of these neuron types within the NTS, with more narrowly tuned cells (Type I) being located more dorsally in the nucleus than the more broadly tuned (Type III) neurons. Cells responding exclusively to touch (Type VI) were also more dorsally situated than those responding to two or more taste stimuli (Types II and III).

Action Potentials↗

Genetic differences in ethanol-induced conditioned taste aversion after ethanol preexposure.

The present studies examined the development of ethanol-induced conditioned taste aversion in C57BL/6J (B6) and DBA/2J (D2) mice with a history of ethanol preexposure. In Experiment 1, adult male B6 and D2 mice received four preexposure injections of either saline or 4 g/kg ethanol over an 8-day period. After preexposure, all mice were given five conditioning trials consisting of 1-h access to 0.15% w/v saccharin solution followed immediately by ethanol injections (4 g/kg, IP) on all but the last trial. Drug-naive D2 mice showed greater reductions in saccharin intake. Ethanol preexposure reduced the development of ethanol-induced taste aversion in each strain. However, B6 mice showed little taste aversion overall, hindering the characterization of genetic differences in ethanol's preexposure effect. To address this problem, the parameters for taste conditioning were changed in Experiment 2 to more closely match degree of taste aversion in drug-naive mice across both strains. B6 and D2 mice received four preexposure injections of either saline, 2 g/kg ethanol, or 4 g/kg ethanol, or 4 g/kg ethanol. Subsequently, mice received five conditioning trials consisting of 1-h access to 0.2 M NaCl flavor followed by 4 g/kg ethanol (B6 mice) or 2 g/kg ethanol (D2 mice) on trials 1-4. Ethanol-naive mice of each strain developed similar levels of conditioned taste aversion. Ethanol preexposure produced greater retardation of conditioned aversion in B6 mice than in D2 mice. These results demonstrate genetic differences in the ability of ethanol preexposure to reduce the development of ethanol-induced conditioned taste aversion.

Animals↗

The effects of lipopolysaccharide and lithium chloride on the ingestion of a bitter-sweet taste: comparing intake and palatability.

Activation of the immune system with lipopolysaccharide (LPS) has been shown to result in decreased consumption of normally preferred substances while at the same time not affecting palatability. The present study examined the effects LPS administration on both intake and palatability of a relatively unpalatable bitter-sweet taste. Bitter is thought to signal a danger cue to an animal representing a potential toxin-containing food. Using a one-bottle consumption test, voluntary intake of a sucrose-quinine (0.15 M sucrose + 0.00015 M quinine; S-Q) solution was assessed in rats on two conditioning days (days 1 and 4) after a systemic injection with LPS, LiCl, or NaCl. On the test day (day 7), rats were given 1h access to the same solution in the absence of any injection. In a separate experiment, rats fitted with intraoral cannulae received similar testing schedules, however, the solution was delivered intraorally, activating only the consummatory responses of the animal. During conditioning, rats received 5 brief (1 min) intraoral infusions of the taste across a 1h period following injections of LPS, LiCl or NaCl. Individual taste reactivity responses were recorded and analyzed. Both LPS and LiCl resulted in decreased consumption of the unpalatable taste relative to controls on the test day, suggesting typical conditioned taste avoidance. When the consummatory responses were examined, LPS-treatment produced an increase in active oral rejection relative to NaCl- and LiCl-treated groups on both conditioning days. The present study demonstrates that although both LPS- and LiCl-treatment result in similar conditioned avoidance using an intake measure, they do not elicit similar patterns of taste reactivity responding to intraoral infusions of the bitter-sweet taste. Furthermore, the present results suggest that immune activation with LPS-treatment results in increased rejection of a mildly aversive stimulus and supports the hypothesis that reorganization of behavioral priorities occurs during bacteria-induced sickness.

Animals↗

Adrenergic drugs modify the level of noradrenaline in the insular cortex and alter extinction of conditioned taste aversion in rats.

We compared the effect of conditioned taste aversion in rats by measuring the amount of sucrose that they drunk after conditioning, which differed according to whether rats had drunk the sucrose freely (SD: self drinking) during the conditioning session, or had been forced to drink it (IO: intra-oral administration through a chronically implanted cannula). The SD procedure delayed the extinction of conditioned taste aversion. Enhanced arousal, alertness, awareness or attention in the SD condition may have strengthened the memory of the taste. Brain noradrenergic networks are involved in such processes. We administered two noradrenergic drugs that produce opposite effects on noradrenaline release in the brain, methoxy-idazoxan, RX821002 (1mg/kg, i.p.), and guanfacine (0.12mg/kg, i.p.). We evaluated their effect (i) on the level of noradrenaline in the gustatory cortex using microdialysis, (ii) on glycaemia that is an essential factor of taste learning and (iii) on the comparative SD versus IO conditioned taste aversion protocol mentioned above. Injecting RX821001 increased the level of noradrenaline in the gustatory cortex up to two-fold of the baseline. This effect lasted 1h. The same dose of RX821002 did not elicit any alteration of glycaemia. It enhanced extinction of conditioned taste aversion in the SD group of rats. Injecting 0.12mg/kg of guanfacine produced the opposite effect. The noradrenaline level of the gustatory cortex decreased, but only down to 20% of the baseline. This decrease lasted 2h. Guanfacine increased glycaemia. Extinction of conditioned taste aversion was only marginally decreased by guanfacine in the SD group of rats. These results fit with Aston-Jones' point of view that the role of the noradrenergic coeruleo-cortical system may be to enhance arousal, alertness, awareness or attention to an event by a transient increase of cortical noradrenaline.

Adrenergic Agents↗

Membrane excitability of wing and rod cells in frog taste discs following denervation.

The frog tongue has a disc-shaped taste organ (taste disc) on the top of fungiform papillae. The taste disc contains two types of cells, wing cells with a sheet-like apical process and rod cells with a rod-like apical process. Both wing and rod cells can produce action potentials. Unlike the taste buds of mammals, frog taste discs do not degenerate over a long period after denervation. Here we report that the shapes of wing and rod cells isolated from taste discs in the bullfrog (Rana catesbeiana) remained unchanged 1 month after cutting bilateral glossopharyngeal nerves. By applying the whole cell patch-clamp technique to isolated wing and rod cells, we found voltage-dependent inward currents and outward currents and action potentials in denervated frogs as seen in normal frogs. These results suggest that the maintenance of morphological integrity and electrical excitability of taste cells does not require a nerve supply in frogs.

Action Potentials↗

Taste representations in the Drosophila brain.

Drosophila taste compounds with gustatory neurons on many parts of the body, suggesting that a fly detects both the location and quality of a food source. For example, activation of taste neurons on the legs causes proboscis extension or retraction, whereas activation of proboscis taste neurons causes food ingestion or rejection. We examined whether the features of taste location and taste quality are mapped in the fly brain using molecular, genetic, and behavioral approaches. We find that projections are segregated by the category of tastes that they recognize: neurons that recognize sugars project to a region different from those recognizing noxious substances. Transgenic axon labeling experiments also demonstrate that gustatory projections are segregated based on their location in the periphery. These studies reveal the gustatory map in the first relay of the fly brain and demonstrate that taste quality and position are represented in anatomical projection patterns.

Animals↗

Predicting food taste with bound-driven optimization.

The prediction of sensory attributes from ingredient-level formulations is an emerging challenge at the intersection of food science and artificial intelligence. We address the fundamental question of whether the taste of a food can be predicted from its ingredients by treating recipes as composite materials. We apply Hashin-Shtrikman (HS) and Reuss-Voigt (RV) bounds, techniques originally developed for elastic moduli, as a null-hypothesis additive baseline for five taste dimensions (sweetness, sourness, bitterness, umami, saltiness) on a curated dataset of 70 recipes decomposed into 115 distinct ingredients scored against a library of 209 ingredient-level taste references with trained-panel ground truth. This baseline systematically under-predicts perceived taste: 77% of actual taste values exceeded the HS upper bound, with the exceedance rate ranging from 26% (bitterness) to 97% (saltiness). We traced this gap to specific processing chemistry (Maillard reactions, caramelization, evaporative concentration, protein hydrolysis, and nucleotide synergy) and introduced a hybrid model that augments the HS baseline with eight chemistry-proxy features encoding these mechanisms. Our results show that our interpretable hybrid model eliminates the systematic bias and reduces mean absolute error by 27%-62% for sweetness, sourness, umami, and saltiness while using only 10 interpretable features, achieving performance comparable to a black-box Lasso regression on 115 per-ingredient features. We further demonstrate constrained inverse design via Differential Evolution, recovering ingredient formulations that match target taste profiles subject to compositional bounds. Our work demonstrates how key chemical processes during food preparation can inform and augment physics-based and machine learning models, providing a quantitative fingerprint of processing chemistry's contribution to taste perception and paving the way for model-driven food formulation with targeted sensory characteristics.

Composite material bounds↗

Aspects of taste and compliance in patients with cancer.

Taste alterations are common in patients with cancer, and can be the result of the disease itself and/or its treatment(s). Specifically, chemotherapy and/or radiotherapy to the head and neck area have been shown to induce significant taste changes. Alterations in taste are distressing for patients and can lead to food aversions, a reduction in food intake and nutritional deficits. Ultimately, this can lead to weight loss and, in severe cases, malnutrition, which has been associated with poor patient outcomes, including a negative effect on survival. Dietary counselling and advice tailored to the individual can improve nutritional status, and several effective strategies are available to accommodate taste changes and increase nutritional intake. Oral supplements may provide additional nutritional support when dietary intake is insufficient. The success of supplementation depends, however, on the product acceptability and on patient compliance over the long term. Patient compliance is linked to perceived supplement taste, which may be affected by a variety of taste changes reported by patients both before and after therapy, or as a consequence of disease progression. Supplements which offer a variety of flavours are likely to prove beneficial by helping to prevent taste fatigue. In addition, individuals appear to exhibit distinct preferences for particular flavours at different time points during treatment.

Antineoplastic Agents↗

Electrophysiologically identified subpopulations of taste bud cells.

The heterogeneous population of mammalian taste cells includes several cellular subtypes specializing in distinct physiological functions. They are poorly understood at the single cell level because the available physiological data have generally been obtained from unidentified taste cells. We recorded them from individual taste cells isolated from circumvallate, foliate, and fungiform papilla of the mouse, employing the patch clamp technique, and tried to elucidate whether universal electrophysiological criteria may be established for the identification of functionally different cellular subpopulations. It was found that irrespective of the papillae type, most ( approximately 96%) of robust taste cells could be categorized into three distinct subgroups on the basis of families of whole-cell (WC) currents exhibited in response to membrane polarization. The validity of this quite simple criterion was further confirmed by using different voltage clamp protocols, ion substitutions, and channel blockers to record different ionic currents, including voltage-gated (VG) Ca(2+), inward-rectifying K(+), and hyperpolarization-activated currents. Given that our findings are based on the statistically significant number of recordings, we believe that the electrophysiological identification of taste cells presented here may be effective for further studies on single taste cell physiology, including taste transduction.

Algorithms↗

Prefrontal activity during taste encoding: an fNIRS study.

To elucidate the function of the lateral prefrontal cortex (LPFC) in taste encoding, it is worth applying to taste, the psychological paradigms of intentional memorization that have been used with other extensively studied senses, and thus updating current models for LPFC functions to include a taste modality. Using multichannel functional near-infrared spectroscopy (fNIRS), we examined the LPFC's of healthy volunteers (N = 18) during the intentional memorization of a basic taste. In order to minimize the confounding effects of verbal processes that are known to employ the left LPFC, we used quaternary taste mixtures that were difficult to verbalize, and confined analysis to those who did not use a verbal strategy during memorization (N = 10). In order to examine the results in association with data in the literature, the location of activity was probabilistically estimated and anatomically labeled in the Montreal Neurological Institute (MNI) standard brain space. By contrasting the cortical activation under encoding conditions with that under control conditions without memory requirement, we found activation in the bilateral ventro-LPFC and the right posterior portion of the LPFC. The activation pattern was consistent with previous studies on the encoding of nonverbal materials using other senses. This suggests that models for LPFC functions that derive from previous studies can be generalized to intentional encoding processes of taste information, at least at a macro-structural level. The current study also demonstrates that, by using fNIRS, LPFC functions on taste can be examined with experimental paradigms relevant to those used for other senses.

Adult↗

Taste bud contains both short-lived and long-lived cell populations.

Taste bud cells undergo continual turnover even in adulthood, and their average lifespan has been estimated as approximately 10 days. However, it is not clear whether this figure can be applied to all the different cell types contained in a taste bud. Here, we describe the age and life cycle of taste bud cells in rat circumvallate papillae, and indicate that the lifespan is heterogeneous, ranging from 2 days to over 3 weeks. Taste bud cells were incorporated from the basal proliferative layer in 1-2 days after birth. After incorporation, approximately half of the cells were eliminated within 2-3 days, and the remaining half were maintained with gradual decrease, suggesting that there are at least two types of cells; short-lived cells and long-lived cells. Moreover, above 10% of the incorporated cells were maintained at 3 weeks. In order to gain information about the relationship between the cell functions and the cell age, we carried out double-labeling experiments using 5-bromo-2'-deoxyuridine and each of two markers for in situ hybridization: mammalian achaete-scute homolog 1 (Mash1) and phospholipase C beta 2 (PLCbeta2) as markers of early differentiation and functional taste signaling, respectively. Mash1 expression began immediately after the incorporation and reached a maximum at 5-6 days after birth. Fewer but distinct Mash1-positive cells were still observed after 3 weeks. PLCbeta2 expression was observed from day 5, reached a maximum at day 12, and continued over 3 weeks. Taken together, a taste bud contains both short-lived and long-lived cells: the short-lived cells are eliminated in a time course similar to the surrounding epithelial cells, and the long-lived cells including taste receptor cells have a lifespan longer than the previous estimation.

Analysis of Variance↗

Multidimensional scaling of ferrous sulfate and basic tastes.

The status of metallic sensations as a primary or basic taste category is controversial. Ferrous sulfate (FeSO4) has been suggested as a prototypical metallic chemosensory stimulus. At least part of the metallic sensation from FeSO4 arises from a metallic retronasal smell. The quality of this sensation was studied via multidimensional scaling (MDS) of taste similarities, with and without nasal closure to eliminate retronasal olfactory sensations. The metallic stimulus was embedded in a series containing classical "basic taste" stimuli, alum and monosodium glutamate. With olfaction available, the metallic stimulus plotted away from basic tastes and taste mixtures. Scaled ratings of sensory properties related to metallic taste (iron-nail, copper-penny-like, aftertaste) of FeSO4 decreased with nasal closure. Results are consistent with the idea that ferrous sulfate produces a distinctly different sensation from the traditional basic tastes, which includes both olfactory and oral sensations.

Adolescent↗

Alterations in taste thresholds in men with chronic obstructive pulmonary disease.

OBJECTIVE: Weight loss is a common occurrence in chronic obstructive pulmonary disease (COPD), and efforts to increase energy intake are often unsuccessful. The objectives of this study were to determine if there were any taste threshold differences between normal-weight and underweight men with COPD, and to determine if there was any association between absolute and recognition taste thresholds and biochemical data associated with COPD. DESIGN: Cross-sectional comparative. SUBJECTS/SETTING: Potential subjects were identified by their physicians. Forty-six men were willing and eligible to participate. Subjects were given sets of triangle taste tests for 4 tastants: sweet, salty, bitter, and sour. Additional information collected included health history data and biochemical data. Subjects were classified as underweight or normal weight for comparison. STATISTICAL ANALYSES PERFORMED: Independent t tests and one-way analysis of variance were used to determine differences between persons in the underweight (n = 17) and normal-weight (n = 29) groups, and the influence of confounding variables. Bivariate correlations were used to determine associations between tastant thresholds and biochemical indexes for the entire group (N = 46). Stepwise regression analysis was used to determine significant variables in prediction of thresholds of the 4 tastants for the entire group (N = 46). RESULTS: Underweight subjects had a significantly higher bitter taste threshold than normal-weight subjects (5.76 vs 5.10, P = .016). A significant negative correlation was found between absolute bitter and bicarbonate (r = -.39, P = .01) and PCO2 (r = -.34, P = .02). A significant regression equation for absolute bitter taste threshold was determined (P = .011) on the basis of bicarbonate values; and upon body mass index for bitter taste recognition threshold (P = .031). APPLICATIONS: Recognition that patients with COPD may have alterations in taste that are associated with weight status and/or biochemical status can guide dietitians in their recommendations for meal plans targeting individual weight goals.

Aged↗

NH3- and CO2-induced suppression of taste nerve responses in clawed toads and eels.

We investigated the effects of intracellular pH values (pHi) on taste nerve responses of clawed toads and eels. (1) CO2, NH3 or trimethylamine reversibly suppressed the taste nerve responses of clawed toads to various amino acids, CaCl2 and caffeine. IC50 values of the suppression of the responses to 0.1 mM L-proline were as follows: approximately 10 mM for CO2, approximately 0.3 mM for NH3, approximately 0.2 mM for trimethylamine. (2) Cross-adaptation experiments showed that L-proline, caffeine and CaCl2 stimulated different receptor sites from each other, indicating the suppressive effect was non-specific. (3) Although CO2, NH3 or trimethylamine yielded the charged molecules, HCO3-, CO3(2-), NH4+ or trimethylammonium on hydration, none of these charged species suppressed taste responses. (4) NH3 increased the threshold concentration of L-proline by e-fold per 0.37 mM NH3 and decreased the maximum response to L-proline with increasing NH3 concentration. (5) The taste nerve responses of eels to 0.1 mM L-arginine, a potent stimulus on eel taste receptors, were similarly suppressed by NH3 with an IC50 value of approximately 0.3 mM. (6) These results indicated that these uncharged species changed pHi, which suppressed the taste responses. CO2-induced acidosis and NH3- or trimethylamine-induced alkalosis are likely to inhibit activities of ion channels or enzymes involved in taste transduction mechanisms.

Ammonia↗